NZ334340A - Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditions - Google Patents

Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditions

Info

Publication number
NZ334340A
NZ334340A NZ334340A NZ33434097A NZ334340A NZ 334340 A NZ334340 A NZ 334340A NZ 334340 A NZ334340 A NZ 334340A NZ 33434097 A NZ33434097 A NZ 33434097A NZ 334340 A NZ334340 A NZ 334340A
Authority
NZ
New Zealand
Prior art keywords
alkyl
group
formula
halo
aryl
Prior art date
Application number
NZ334340A
Inventor
Dinanath F Rane
Alan K Mallams
Arthur G Taveras
F George Njoroge
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Publication of NZ334340A publication Critical patent/NZ334340A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

Abstract

The use of compounds represented by formula I as farnesyl transferase protein inhibitors. The tricyclic compounds disclosed does not inhibit geranylgeranyl protein transferase I, in vitro, as it appears to block the phenotypic change induced by a form of transforming Ras engineered to be a geranylgeranyl acceptor, blocks intracellular processing of Ras which is a farnesyl acceptor but not of a Ras engineered to be a geranylgeranyl acceptor and it blocks abnormal cell growth in cell culture induced by transforming Ras. The pharmaceutical composition is useful for inhibiting abnormal cell growth, such as tumours. Wherein; One of a, b, c and d represents N or NR9 wherein R9 is O-, -CH3 or -(CH2)nCO2H wherein n is 1 to 3, and the remaining a, b, c and d groups represent CR1 or CR2; or a, b, c, and d are independently selected from the group consisting of CR1 and CR2; wherein R1 and R2 are independently selected from the group consisting of H, halo, -CF3, -OR10, -COR10, -SR10, -S(O)tR11 wherein t is 0,1 or 2, -SCN, -N(R10)2, -NR10R11, -NO2, -OC(O)R10, -C02R10, -OCO2R11, -CN, -NHC(O)R10, -NHSO2R10, -CONHR10, -CONHCH2CH2OH, -NR10COOR11, Formula II, -SR11C(O)OR11, -SR11N(R75)2, wherein each R75 is independently selected from H and -C(O)OR11, benzotriazol-1-yloxy, tetrazol-5-ylthio, substituted tetrazol-5-ylthio, alkynyl, alkenyl and alkyl, R3 and R4 are independently selected from the group consisting of H, R1 and R2, or R3 and R4 taken together represent a saturated or unsaturated C5-C7 fused ring to the benzene ring; R5, R6, R7 and R8 are independently selected from the group consisting of H, -CF3, -COR10, alkyl and aryl, and R10 represents H, alkyl, aryl, or aralkyl; X represents N, CH or C, which C may contain an optional double bond (represented by the dotted line) to carbon atom 11; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently are selected from the group consisting of -R10, halo, -OR11, -OC02R11 and -OC(O)R10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent (H, H), (OR11, -OR11), (H, halo), (halo, halo), (alkyl, H), (alkyl, alkyl), (H, -OC(O)R10), (H, -OR10), =O, (aryl, H) and =NOR10, or A and B together are -O-(CH2)p-O- wherein p is 2, 3 or 4; and R represents: (1) -C(O)N(R10)2; (2) -CH2C(O)N(R1 )2; (3) -SO2-alkyl, -SO2-aryl, -S02-aralkyl, -SO2-heteroaryl or -SO2 heterocycloalkyl; (4) cyano; (5) an imidate represented by the formula III; (6) an imidamido group of the formula IV; (7) a 1-amino-2-nitroethylene derivative of the formula V; (8) -C(O)R16; (9) -O(O)-O-R16; (10) Formula VI; (11) alkyl, aryl. aralkyl, cycloalkyl, heterocycloalkyl or heteroaryl; (12) -S02NR10R14; (13) -P(O)(R10)2; (14) a sugar group of the formula VII, VIII, IX; (15) -CH2C(O)OR28.
NZ334340A 1996-09-13 1997-09-11 Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditions NZ334340A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US71332696A 1996-09-13 1996-09-13
PCT/US1997/015900 WO1998011096A1 (en) 1996-09-13 1997-09-11 Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases

Publications (1)

Publication Number Publication Date
NZ334340A true NZ334340A (en) 2000-09-29

Family

ID=24865700

Family Applications (1)

Application Number Title Priority Date Filing Date
NZ334340A NZ334340A (en) 1996-09-13 1997-09-11 Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditions

Country Status (21)

Country Link
EP (1) EP0927178B1 (en)
JP (1) JP3152438B2 (en)
KR (1) KR20000036059A (en)
CN (1) CN1237169A (en)
AT (1) ATE213736T1 (en)
AU (1) AU729810B2 (en)
BR (1) BR9712819A (en)
CA (1) CA2264569C (en)
CZ (1) CZ83499A3 (en)
DE (1) DE69710741T2 (en)
ES (1) ES2169420T3 (en)
HK (1) HK1018267A1 (en)
HU (1) HUP9904067A2 (en)
ID (1) ID22045A (en)
IL (1) IL128949A0 (en)
NO (1) NO991230L (en)
NZ (1) NZ334340A (en)
PL (1) PL332240A1 (en)
SK (1) SK33199A3 (en)
TR (1) TR199900561T2 (en)
WO (1) WO1998011096A1 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2318088A1 (en) 1998-01-21 1999-07-29 Yoshisuke Nakasato Chemokine receptor antagonists and methods of use therefor
US6613905B1 (en) 1998-01-21 2003-09-02 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
ATE309249T1 (en) 1998-01-21 2005-11-15 Millennium Pharm Inc CHEMOKINE RECEPTOR ANTAGONISTS AND USES
US6509346B2 (en) 1998-01-21 2003-01-21 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
US7271176B2 (en) 1998-09-04 2007-09-18 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use thereof
US6503926B2 (en) 1998-09-04 2003-01-07 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
US6288083B1 (en) 1998-09-04 2001-09-11 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
US7541365B2 (en) 2001-11-21 2009-06-02 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
TWI291467B (en) 2002-11-13 2007-12-21 Millennium Pharm Inc CCR1 antagonists and methods of use therefor
EP1656156A2 (en) 2003-08-13 2006-05-17 Children's Hospital Medical Center Mobilization of hematopoietic cells
ATE524445T1 (en) 2005-06-23 2011-09-15 Merck Sharp & Dohme BENZOCYCLOHEPTAPYRIDINES AS INHIBITORS OF TYROSINE KINASE MET
TW200813021A (en) 2006-07-10 2008-03-16 Merck & Co Inc Tyrosine kinase inhibitors
TW201024283A (en) * 2008-12-01 2010-07-01 Targacept Inc Synthesis and novel salt forms of (R)-3-((E)-2-(pyrrolidin-3-yl)vinyl)-5-(tetrahydropyran-4-yloxy)pyridine
EP3519385B1 (en) 2016-09-27 2020-11-18 Mission Therapeutics Limited Cyanopyrrolidine derivatives with activity as inhibitors of usp30

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUT76057A (en) * 1993-10-15 1997-06-30 Schering Corp Tricyclic sulfonamide compounds, pharmaceutical compositions containing them, which are useful for inhibition of g-protein function and for treatment of proliferative diseases and process for producing them
IL111235A (en) * 1993-10-15 2001-03-19 Schering Plough Corp Pharmaceutical compositions for inhibition of g-protein function and for treatment of proliferative diseases containing tricyclic compounds some such compounds and process for preparing part of them
ATE210652T1 (en) * 1993-10-15 2001-12-15 Schering Corp TRICYCLIC CARBAMAT DERIVATIVES FOR INHIBITING G-PROTEIN FUNCTION AND FOR THE TREATMENT OF PROLIFERATIVE DISEASES

Also Published As

Publication number Publication date
NO991230D0 (en) 1999-03-12
WO1998011096A1 (en) 1998-03-19
AU729810B2 (en) 2001-02-08
BR9712819A (en) 1999-11-23
AU4337397A (en) 1998-04-02
KR20000036059A (en) 2000-06-26
IL128949A0 (en) 2000-02-17
JP3152438B2 (en) 2001-04-03
HUP9904067A2 (en) 2000-05-28
CN1237169A (en) 1999-12-01
NO991230L (en) 1999-05-14
CZ83499A3 (en) 1999-07-14
ES2169420T3 (en) 2002-07-01
ID22045A (en) 1999-08-26
HK1018267A1 (en) 1999-12-17
CA2264569A1 (en) 1998-03-19
DE69710741T2 (en) 2002-10-24
EP0927178B1 (en) 2002-02-27
ATE213736T1 (en) 2002-03-15
DE69710741D1 (en) 2002-04-04
CA2264569C (en) 2003-11-11
PL332240A1 (en) 1999-08-30
SK33199A3 (en) 1999-12-10
JP2000502727A (en) 2000-03-07
TR199900561T2 (en) 1999-06-21
EP0927178A1 (en) 1999-07-07

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